Edward H. Wood, MD: Pharmacodynamics of Subretinal RGX-314 for Wet AMD

Subretinal delivery of investigational ABBV-RGX-314 gene therapy provided by the NAVXpress bioreactor platform was well-tolerated with a similar clinical profile to the adherent cell culture process, according to Phase II pharmacodynamic study data.¹

These Phase 2 pharmacodynamic results, presented at the American Society of Retina Specialists (ASRS) 42nd Annual Meeting, reinforce the ongoing ATMOSPHERE and ASCENT pivotal trials in patients with neovascular age-related macular degeneration (nAMD).

“Not only from this study do we get evidence that the manufacturing process is similar and expected, we also get an early look at how these data might look from the ongoing pivotal trials, given the protocol and dose levels are the same,” presenting investigator Edward H. Wood, MD, Austin Retina Associates told HCPLive. “It's one of the more exciting ways that we're looking at gene therapy for our field.”

RGX-314 is an investigational single-administration gene therapy that delivers a transgene for a soluble anti-vascular endothelial growth factor (VEGF) Fab. This Phase 2 pharmacodynamic bridging study in nAMD assessed the clinical performance between subretinal RGX-314 produced with REGENXBIO’s proprietary NAVXpress bioreactor platform process and an initial adherent cell culture manufacturing process used in the Phase 1/2a trial.

Overall, 60 patients were assigned to two dose levels: 6.4/1010 GC/eye or 1.3/1011 GC/eye. Half of the population received the bioreactor process and the other half received the adherent cell culture manufacturing process. Protein concentration of RGX-314 in the eye at Month 6 served as the primary endpoint.

By May 2023, RGX-314 was well-tolerated across all cohorts. Five serious adverse events were reported, but none were believed to be related to the study drug. RGX-314 protein concentrations in the study eye were similar across 6 months in the high-dose (n = 30) and low-dose (n = 15) cohorts.

In addition, both study cohorts demonstrated stable-to-improved best-corrected visual acuity (BCVA) and central retinal thickness (CRT), and meaningful reductions in anti-VEGF burden. Many patients (67–77%) remained injection-free and there was a 68–86% reduction in the need for supplemental anti-VEGF therapy.

These initial study results support dose levels and Current Good Manufacturing Practice (cGMP) commercial-ready materials evaluated in the ongoing ATMOSPHERE and ASCENT pivotal trials.

“I think as we're gathering more data, we'll have more long-term answers that we're all looking for, but this specific look at the Phase 2 pharmacodynamic study was compelling,” Wood told HCPLive.

Disclosures: Relevant disclosures for Wood include Genentech, RegenXBio, Pharming, Allergan, and Iveric Bio.

Reference

_{Wood EH. Subretinal Delivery of Investigational ABBV-RGX-314 for Neovascular Age-Related Macular Degeneration: A Phase II Pharmacodynamic Study. Paper presented at the American Society of Retina Specialists (ASRS) 42nd Annual Meeting. Stockholm, Sweden. July 17-20, 2024.}